Our objectives are to study in detail the structure of relaxin genes in man, mouse, sheep and pig; to carry out gene transfer studies in order to study the regulation of relaxin gene expression; to locate the tissue sites and cell types producing relaxin; to study the mode of relaxin precursor processing and to characterize the processing enzymes; to determine the key structural features of the relaxin molecule important for biological activity; to determine the tertiary structure of relaxin; to develop homologous radioimmunoassays for human relaxin and for the relaxin C peptide; to measure relaxin and C peptide in blood and tissue fluids in pregnant and non-pregnant females and in males; to measure relaxin levels in complicated human pregnancy. The main techniques involved will be those of recombinant DNA, particularly gene transfer methods, and peptide chemistry particularly solid phase peptide synthesis and high resolution N.M.R. A technique developed in our laboratory for localization of specific new mRNA in whole tissue sections (hybridization histochemistry) will be used to localize sites of relaxin gene transcription. These studies should advance our understanding of the physiology of relaxin, particularly in human pregnancy and provide a sound basis for the later conduct of clinical trials of relaxin in prevention and treatment of difficult labour and premature onset of labor. Since relaxin has major effects on collagen and on uterine smooth muscle these studies are also directly relevant to conective tissue disorders and to the control of uterine contractility and compliance.